Zilpaterol is a known adrenergic β-2 agonist having the following structure:
The IUPAC name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino)imidazo[4,5,1-jk]-[1]benzazepin-2(1H)-one. The Chemical Abstracts name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methyl-ethyl) amino]-imidazo [4,5,1-jk][1]benzazepin-2(1H)-one.
Zilpaterol has two chiral carbons:
Consequently, zilpaterol has four optical enantiomers. These enantiomers are identified as “(6R,7R),” “(6R,7S),” “(6S,7R),” and “(6S,7S).” CAS No. 119520-05-7 corresponds to racemic trans zilpaterol (i.e., a mixture of the (6R,7R) and (6S,7S) enantiomers), and has been identified in the literature as “RU42173.” The trans enantiomers have the following structures:

Zilpaterol is well known in the art.
For example, in U.S. Pat. No. 4,585,770, Fréchet et al. discuss compounds encompassed by a genus characterized as 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-j-k][1]-benzazepin-2-(1H)-one derivatives, and, in particular, derivatives (and pharmaceutically acceptable acid addition salts thereof) corresponding to the following structure:
Here, R can be various substituents, and the wavy lines indicate that the bonds to the 6-amino and 7-OH groups have the trans configuration. This genus encompasses racemic trans zilpaterol when R is isopropyl. Fréchet et al. state that such compounds may be used as an active ingredient for inducing antihypertensive and hypotensive activity in a warm-blooded animal.
In U.S. Pat. No. 4,900,735, Grandadam discusses a zootechnical composition comprising at least one compound of the following formula or a pharmaceutically acceptable acid addition salt thereof:
Here, R can be various substituents, and the wavy lines indicate that the bonds to the 6-amino and 7-OH groups have the trans configuration. As with the genus discussed in U.S. Pat. No. 4,585,770, this genus encompasses racemic trans zilpaterol when R is isopropyl. Grandadam states that such a composition may be used to increase the weight of cattle, pigs, or poultry, and may optionally further comprise a steroid.
In U.S. Pat. Nos. 5,731,028 and 5,847,124, Chevremont et al. discuss crystallized anhydrous zilpaterol hydrochloride, and particularly crystallized anhydrous zilpaterol hydrochloride wherein less than 5% of the crystals have a size of less than 15 μm, and at least 95% of the crystals have a size of less than 250 μm. According to Chevremont et al., such crystals may be incorporated into animal feed to increase body weight and meat quality. Chevremont et al. provide methods for making such crystals, and discuss using the crystals to make animal premixes in which the crystals are secured to a corn cob support having a greater particle size. They also discuss monohydrate and trihydrate intermediates that can be useful in, for example, making the crystals.
In U.S. Pat. No. 7,207,289, Montgomery discusses methods for increasing beef production, reducing feed intake while maintaining beef production, and reducing incidences of liver abscess in cattle. These methods comprise administering a feed comprising an ionophore and macrolide antibiotic during an initial period, and then administering a feed comprising zilpaterol with essentially no ionophore or macrolide antibiotic.
There has been some discussion in the art relating to enantiomers of various adrenergic β-2 agonists. Such discussion may be found in, for example, U.S. Pat. No. 6,110,974; U.S. Patent Appl. Publ. 2005/0113456; and U.S. Patent Appl. Publ. 2002/0132830.
There still exists a need for alternative compositions and methods for increasing the rate of weight gain, improve feed efficiency, and/or increase carcass leanness in livestock, poultry, and/or fish. The following disclosure describes such compositions and methods.